A. Studies have been done to clarify the relationship between cell cycle regulation and DNA repair in hamster cells: 1) UV irradiation of G1-synchronized cells causes a dose-dependent, p53-independent delay of entry into S phase. UV irradiation of G2-synchronized cells also causes a dose- and time-dependent delay before passage into the subsequent G1 phase. 2) Repair of cyclobutane pyrimidine dimers occurs with identical compartmentalization and equal efficiency during G1 and G2 phases. 3) An extended late S/G2 arrest observed after S phase UV irradiation results in apoptosis. 4) Delays in completion of replication, extended G2 arrest, and apoptosis were caused by the persistence of UV-induced DNA damage. 5) UV-induced 6-4 photoproducts are a much greater hindrance to replication than pyrimidine dimers. 6) Transcription of ERCC1, a gene involved in DNA repair and recombination, is elevated in late S and G2 phases in comparison to other periods of the cell cycle. Other repair genes studied (XPB, XPD, and CS-B) appear to be expressed at the same level throughout the cell cycle. B. Preferential, gene specific DNA repair occurs at the nuclear matrix, where transcription also is maximal. There is no coupling between transcription and repair in ribosomal DNA. C. In resting human CD4 lymphocytes, there is little or no repair in the essential gene DHFR. In proliferating lymphocytes we find both transcription associated gene specific repair increases and gene specific repair of genes that are not transcribed. The latter result suggests a connection between repair efficiency and the replicative status of the cell or DNA region. D. The repair of an episomal extra chromosomal gene is less efficient than repair of an endogenous gene.